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Biomedical subjects

M Bentz

Publications and source records attributed to M Bentz.

At least 19 recordsLinked to original sources
PubMed2003

DNA microarray analysis in malignant lymphomas.

Recently, DNA microarray technology has opened new avenues for the understanding of lymphomas. By hybridization of cDNA to arrays containing >10,000 different DNA fragments, this approach allows the simultaneous evaluation of the mRNA expression of thousands of genes in a single experiment. Using sophisticated bioinformatic tools, the huge amount of raw data can be clustered resulting in (1) tumor subclassification, (2) identification of pathogenetically relevant genes, or (3) biological predictors for the clinical course. This approach already has provided novel insights into different entities of B-cell non-Hodgkin's lymphomas. Genomic DNA chip hybridization (matrix-CGH) is a complementary approach focussing on genomic aberrations. In this review, we discuss the impact of this new technology both with regard to methodological aspects as well as to novel findings influencing our understanding of lymphomas.

Gene Expression Profiling↗
PubMed2003

Induction by sphingomyelinase of shiga toxin receptor and shiga toxin 2 sensitivity in human microvascular endothelial cells.

Shiga toxin-producing enterohemorrhagic Escherichia coli is the major cause of acute renal failure in young children. The interaction of Shiga toxins 1 and 2 (Stx1 and Stx2) with endothelial cells is an important step in the renal coagulation and thrombosis observed in hemolytic uremic syndrome. Previous studies have shown that bacterial lipopolysaccharide and host cytokines slowly sensitize endothelial cells to Shiga toxins. In the present study, bacterial neutral sphingomyelinase (SMase) rapidly (1 h) sensitized human dermal microvascular endothelial cells (HDMEC) to the cytotoxic action of Stx2. Exposure of endothelial cells to neutral SMase (0.067 U/ml) caused a rapid increase of intracellular ceramide that persisted for hours. Closely following the change in ceramide level was an increase in the expression of globotriaosylceramide (Gb3), the receptor for Stx2. A rapid increase was also observed in the mRNA for ceramide:glucosyltransferase (CGT), the first of three glycosyltransferase enzymes of the Gb3 biosynthetic pathway. The product of CGT (glucosylceramide) was also increased. In contrast, mRNA for the third enzyme of the pathway, Gb3 synthase, was constitutively produced and was not influenced by SMase treatment of HDMEC. These results describe a rapid response mechanism by which extracellular neutral SMase derived from either bacteria or eukaryotic cells may signal endothelial cells to become sensitive to Shiga toxins.

Cells, Cultured↗
PubMed2001

Clinical relevance of genomic aberrations in homogeneously treated high-risk stage II/III breast cancer patients.

Little is known about the prognostic impact of chromosome aberrations in breast cancer. The aim of our study was to determine whether genomic aberrations of prognostic relevance can be identified in the context of a clinical study using molecular cytogenetics. Paraffin-embedded tumor samples of 44 patients with high-risk stage II/III breast cancer were analyzed by comparative genomic hybridization. All patients received identical therapy including dose-escalated chemotherapy followed by peripheral blood stem cell transplantation. The most frequent chromosomal aberrations were gains on chromosome arms 17q (24 cases), 1q (21 cases), 8q (17 cases), 20q (13 cases), 6p (9 cases) as well as losses on chromosome arms 13q (25 cases), 11q (20 cases), 5q (11 cases), 6q (11 cases), 9p (10 cases), 18q (10 cases), 8p (9 cases) and 16q (9 cases). In univariate analysis, the correlation with the clinical outcome revealed a higher risk for patients with tumors exhibiting 13q losses and a reduced risk for tumors exhibiting 16q losses (p = 0.020), 6q losses (p = 0.041) and estrogen-receptor positivity (0.051). In multivariate analysis using the Cox model, only the loss of 16q exhibited borderline significance (p = 0.065). These data show that comparative genomic hybridization can be performed in the context of a clinical trial. In our subgroup of high-risk breast cancer patients, chromosomal aberrations were valuable prognostic parameters.

Adult↗
PubMed2001

Gain of chromosome arm 9p is characteristic of primary mediastinal B-cell lymphoma (MBL): comprehensive molecular cytogenetic analysis and presentation of a novel MBL cell line.

Primary mediastinal B-cell lymphoma (MBL) is an aggressive Non-Hodgkin's Lymphoma, which has been recognized as a distinct disease entity. We performed a comprehensive molecular cytogenetic study analyzing 43 MBLs. By comparative genomic hybridization (CGH), the most common aberrations were gains of chromosome arms 9p and Xq, which were present in 56% and 40% of cases, respectively. Based on the limited resolution of CGH, this technique may underestimate the real incidence of aberrations. Therefore, we also did an interphase cytogenetic study with eight DNA probes mapping to chromosome regions frequently altered in B-cell lymphomas. With this approach, both 9p and Xq gains were found in more than 70% of cases (75% and 87%, respectively). The findings were compared with results obtained in 308 other B-cell lymphomas. Gains in 9p were identified in only six of the 308 cases, and only one of these lymphomas with 9p gains was not primarily extranodal in origin (P < 10-(20) for CGH data and P < 10-(11) for fluorescence in situ hybridization data). We also present a novel MBL cell line, MedB-1, which carries the genetic aberrations characteristic of this entity.

Adolescent↗
PubMed2001

Molecular-cytogenetic comparison of mucosa-associated marginal zone B-cell lymphoma and large B-cell lymphoma arising in the gastro-intestinal tract.

Extranodal B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) type may represent a model of lymphoma progression, because a small cell component frequently occurs in the large cell variants. We studied 52 extranodal B-cell lymphomas: 18 extranodal marginal zone B-cell lymphomas of MALT type (MZBL,MT), 7 MZBL,MT of the gastro-intestinal tract with a diffuse large B-cell component (giMZBLplusLBCL), and 27 diffuse large B-cell lymphomas of the gastro-intestinal tract without small cell component (giLBCL). Analytical techniques were comparative genomic hybridization (CGH) and fluorescence in situ hybridization (FISH). The translocation t(11;18) was found as the sole aberration in two MZBL,MT only. In contrast to this, t(11;18)-negative MZBL,MT were characterized by frequent gains on chromosome 3 and DNA amplifications on 2p13-p15. Furthermore, we found a clonal lymphoma progression from the small to the large cell component with accumulation of gains and losses of chromosomal material in the large cell component in giMZBLplusLBCL. Aberrations overlapping with MZBL,MT and giMZBLplusLBCL included losses on chromosome 13, amplifications of the REL proto-oncogene, or gains on chromosome 12. In addition, the large cell component revealed gains on 8q24, including amplifications of the MYC proto-oncogene, and losses on 2q. The giLBCL had frequent gains on chromosomes 12 and 9, as well as on 11q, and losses on 6q. We conclude that, based on the distinctive and partly overlapping patterns of genetic aberrations, MALT lymphomas can be divided into different genetic subgroups.

Chromosome Aberrations↗
PubMed2001

Detection of secondary genetic aberrations in follicle center cell derived lymphomas: assessment of the reliability of comparative genomic hybridization and standard chromosome analysis.

Secondary chromosomal aberrations in follicle center cell derived lymphomas (FCDL) usually involve gains and losses of genetic material and may be an important prognostic value. In the present study, we aimed to determine the power of comparative genomic hybridization (CGH) as compared to standard chromosome analysis (CA) to detect such secondary aberrations. The same lymph node cell suspensions prepared from 30 patients with FCDL were analyzed in parallel by CGH and CA based on R banding. In all, 73 discrepancies were found. Sixty-two imbalances were detected only by CA and 11 only by CGH. In cases with completely resolved karyotypes (n= 17), the median number of discrepancies between CGH and CA was one. However, when the karyotype was partially resolved (n = 12), the median was four (P < 0.01). Discrepant results were further studied by fluorescence in situ hybridization using locus-specific probes. These data confirm, that not only for the detection of balanced aberrations, but also for the detection of unbalanced aberrations in FCDL, standard chromosome analysis is still the 'gold standard'. In contrast, CGH is useful to detect chromosomal imbalances when no metaphases are found or no fresh material is available.

Chromosome Aberrations↗
PubMed2001

Renal cell carcinoma metastatic to the scalp: case report and review of the literature.

BACKGROUND: Renal cell carcinoma metastatic to the skin is rare. OBJECTIVE: To illustrate by a case report the clinical presentation and management of the disease. METHODS: We present a case of renal carcinoma metastatic to the skin of the scalp that occurred 6 years after removal of her kidney. The tumor was diagnosed using frozen tissue and paraffin sections. RESULTS: Cutaneous metastasis treated by excision. CONCLUSION: Renal cell carcinoma may metastasize to the skin of the scalp. Our case illustrated an interesting ipsilateral metastasis that occurred 6 years after treatment of her primary tumor. Physicians, dermatologists, pathologists, and Mohs surgeons should be aware of this entity.

Aged↗
PubMed2001

Merkel cell carcinoma of the skin and mucosa: report of 12 cutaneous cases with 2 cases arising from the nasal mucosa.

BACKGROUND: Merkel cell carcinoma (MCC) is an uncommon skin tumor that most frequently arises on sun-exposed facial sites. It rarely occurs on mucous membranes of the head region. The primary MCC is usually treated by wide excision followed by radiation to the primary site and regional lymph nodes. Using traditional surgery the local recurrence rate ranges from 20 to 50%. In our clinic, Mohs surgery is used to excise the primary MCC completely, followed by radiation. Here we present our treatment experiences and outcomes. OBJECTIVE: To document our experience of MCC treated by Mohs surgery. We present our series of 12 cases of MCC, 2 cases of which arose from mucosal sites of the nasal cavity. METHODS: We reviewed 12 cases of MCC from the Mohs clinic database. We also reviewed the literature for cutaneous and mucosal MCC. RESULTS: There were 12 cases of MCC: 10 cutaneous and 2 mucous. The site distribution of cutaneous MCC was eight on the head, one on the neck, and one on the groin. Of these, nine were treated by Mohs excision. Two patients developed local recurrence following Mohs treatment. The local recurrence rate was 22% (2 of 9). The sites of mucosal MCC were the nasal septum and nasopharynx. One case had a history of previous radiation and developed an MCC 40 years later. This case also demonstrated epidermotropic spread of Merkel cells to the overlying mucous epithelium. This patient required extensive intranasal and cranial surgery to remove the tumor. Both patients with mucosal MCCs died of their disease. The overall mucocutaneous survival of MCC at 1 year was 80% and at 2 years was 50%. CONCLUSION: In our series, local control of the primary MCC was achieved in 70% of patients (7 of 10) using combined Mohs excision and radiation. Two recurrences had primary tumors larger than 3.5 cm in diameter, while the other case was nonresectable by Mohs surgery. Tumor size appeared to determine the degree of local control. When the postoperative Mohs defect was less than 3.0 cm in diameter, local and regional control appeared to be more favorable. When the primary facial MCC is relatively small, removal by Mohs surgery followed by radiation was effective, therapeutic, and less disfiguring. Mucosal MCC is rare and may occur as a long-term sequelae after radiation therapy to the skin.

Aged↗
PubMed2001

Microcystic adnexal carcinoma: report of 13 cases and review of the literature.

BACKGROUND: Microcystic adnexal carcinoma (MAC) is a rare tumor of the skin. Clinically it often masquerades as a firm, subcutaneous nodule on the head and neck regions. Microscopically it extends far beyond assessed clinical margins spreading locally in the dermal, subcutaneous, and perineural tissue planes. The local recurrence rate by standard excision is about 50%. Recent preliminary reports indicate more favorable cure rates with Mohs micrographic surgery (MMS). OBJECTIVE: To present our data on 13 cases (12 patients) of MAC treated by MMS. In addition, we reviewed the medical literature to summarize the accumulated experience of MMS treatment in the management of MAC. We also present a case of bilateral MAC of the face and describe a renal transplant recipient on immunosuppressive therapy who developed MAC of the nasal bridge. METHODS: We reviewed and updated our series of MAC cases treated by MMS over the last 9 years. A total of 13 cases of MAC are reviewed. We also searched the literature for MAC treated by MMS with a follow-up of more than 2-years. RESULTS: One patient had bilateral MAC of the nose and cheek. Another patient developed a MAC of the nasal bridge 20 years after renal transplantation. In this patient predisposing factors were radiation for teenage acne and immunosuppression therapy. A total of 13 cases of MAC were treated by MMS with no recurrences, with a mean follow-up of 5.0 years (range 1.1-8.0 years). CONCLUSION: We update the medical literature with 13 MAC cases treated by MMS. To our knowledge there have been 148 cases of MAC reported in the world literature. Including our series, there have been 73 cases of MAC treated with MMS. There were only four treatment failures. Regional and/or distant metastasis from MAC is rare, with only one reported death. Following MMS, the 2-year success rate was 89.7% (35 of 39). The accumulated data continue to confirm that when MAC is discovered early and is readily accessible to excision by MMS and other subspecialty support, a favorable outcome can be expected.

Adult↗
PubMed2001

Molecular aspects of B-cell lymphomas of the gastrointestinal tract.

The B-cell lymphomas of the gastrointestinal (GI) tract have represented a field of extensive research ever since a close association was shown with such chronic inflammatory processes as Helicobacter pylori infection. Evidence suggested that the mucosa-associated lymphoid tissue induced by inflammation and autoimmune processes is the environment that gives rise to the small-cell lymphomas of the GI tract (eg, extranodal marginal zone B-cell lymphoma according to Revised European-American Classification of Lymphoid Neoplasms and the World Health Organization Classification of Neoplastic Diseases of the Hematopoietic and Lymphoid Tissue). The small B-cell lymphoma may then progress to highly malignant variants. The B-cell lymphomas of the GI tract may present a stepwise model for lymphomagenesis and progression. This review covers molecular biology and molecular cytogenetic aspects that lead to new insights into the biology of GI lymphomas and potential prognostic factors.

Cell Transformation, Neoplastic↗
PubMed2000

Genomic aberrations and survival in chronic lymphocytic leukemia.

BACKGROUND: Fluorescence in situ hybridization has improved the detection of genomic aberrations in chronic lymphocytic leukemia. We used this method to identify chromosomal abnormalities in patients with chronic lymphocytic leukemia and assessed their prognostic implications. METHODS: Mononuclear cells from the blood of 325 patients with chronic lymphocytic leukemia were analyzed by fluorescence in situ hybridization for deletions in chromosome bands 6q21, 11q22-23, 13q14, and 17p13; trisomy of bands 3q26, 8q24, and 12q13; and translocations involving band 14q32. Molecular cytogenetic data were correlated with clinical findings. RESULTS: Chromosomal aberrations were detected in 268 of 325 cases (82 percent). The most frequent changes were a deletion in 13q (55 percent), a deletion in 11q (18 percent), trisomy of 12q (16 percent), a deletion in 17p (7 percent), and a deletion in 6q (7 percent). Five categories were defined with a statistical model: 17p deletion, 11q deletion, 12q trisomy, normal karyotype, and 13q deletion as the sole abnormality; the median survival times for patients in these groups were 32, 79, 114, 111, and 133 months, respectively. Patients in the 17p- and 11q-deletion groups had more advanced disease than those in the other three groups. Patients with 17p deletions had the shortest median treatment-free interval (9 months), and those with 13q deletions had the longest (92 months). In multivariate analysis, the presence or absence of a 17p deletion, the presence or absence of an 11q deletion, age, Binet stage, the serum lactate dehydrogenase level, and the white-cell count gave significant prognostic information. CONCLUSIONS: Genomic aberrations in chronic lymphocytic leukemia are important independent predictors of disease progression and survival. These findings have implications for the design of risk-adapted treatment strategies.

Adult↗
PubMed2000

Portosystemic shunting and persistent fetal vascular structures in aryl hydrocarbon receptor-deficient mice.

A physiological examination of mice harboring a null allele at the aryl hydrocarbon (Ah) locus revealed that the encoded aryl hydrocarbon receptor plays a role in the resolution of fetal vascular structures during development. Although the aryl hydrocarbon receptor is more commonly studied for its role in regulating xenobiotic metabolism and dioxin toxicity, a developmental role of this protein is supported by the observation that Ah null mice display smaller livers, reduced fecundity, and decreased body weights. Upon investigating the liver phenotype, we found that the decrease in liver size is directly related to a reduction in hepatocyte size. We also found that smaller hepatocyte size is the result of massive portosystemic shunting in null animals. Colloidal carbon uptake and microsphere perfusion studies indicated that 56% of portal blood flow bypasses the liver sinusoids. Latex corrosion casts and angiography demonstrated that shunting is consistent with the existence of a patent ductus venosus in adult animals. Importantly, fetal vascular structures were also observed at other sites. Intravital microscopy demonstrated an immature sinusoidal architecture in the liver and persistent hyaloid arteries in the eyes of adult Ah null mice, whereas corrosion casting experiments described aberrations in kidney vascular patterns.

Animals↗
PubMed2000

Genomic imbalances including amplification of the tyrosine kinase gene JAK2 in CD30+ Hodgkin cells.

Comparative genomic hybridization was applied for a comprehensive screening of frequently occurring net gains and losses of chromosomal subregions in small populations of CD30+ Hodgkin cells and their morphological variants. In 12 Hodgkin's lymphomas, recurrent gains were detected on chromosomal arms 2p, 9p, and 12q (in six, four, and five tumors, respectively) and distinct high-level amplifications were identified on chromosomal bands 4p16, 4q23-q24, and 9p23-p24. In Hodgkin cells with 9p23-p24 amplification, fluorescence in situ hybridization revealed an increased copy number of chromosomal sequences spanning the tyrosine kinase gene JAK2. Several of the imbalances described, in particular a gain in chromosomal arm 9p that includes JAK2 amplification, are similar to the genomic changes detected in primary mediastinal B-cell lymphoma.

Adolescent↗
PubMed2000

Risk of false positive results in comparative genomic hybridization.

Comparative genomic hybridization, a widely used method for screening for genomic imbalances, suffers from a lack of standardized evaluation. In order to compare a recently proposed data-driven procedure with the commonly used fixed cutoff values, we tested 257 events by both procedures as well as by fluorescence in situ hybridization using selected probes. With the data-driven procedure, a much higher fraction (42/218 vs. 8/218) of false positive results was obtained, whereas a higher sensitivity with respect to the detection of imbalances (30/39 vs. 19/39) was reached. Based on the significantly higher positive likelihood ratios and the positive predictive value, we strongly recommend the use of fixed diagnostic thresholds, because the alternative procedure generates an unacceptably high portion of incorrectly scored chromosomal imbalances. Genes Chromosomes Cancer 28:353-357, 2000.

Chromosome Aberrations↗
PubMed2000

Primary gastric apoptosis-rich T-cell lymphoma co-expressing CD4, CD8, and cytotoxic molecules.

In contrast to primary gastric lymphomas of B-cell type, little is known about primary gastric T-cell lymphomas. We describe three cases with remarkably similar features: diffuse growth, epitheliotropism, medium too large cell size, high apoptotic rates, and a CD3+, CD4+, CD8+, CD45RO+ immunophenotype. Clonal TCRgamma gene rearrangement was shown in two cases. Epstein-Barr virus infection was excluded in two cases. Taking advantage of fresh-frozen material, we analyzed two cases further, revealing CD5-, CD16+, CD56-, CD57-, CD25+, CD30+, CD103 (alphaEbeta7)+, bcl-2 protein+, CD95+, CD95 ligand(L)-. CD95L, however, was detected in histiocytic and fibroblastoid by stander cells. The lymphomas expressed granzyme B, perforin, and the TIA-1 antigen in various combinations. All three cases had a very unfavorable clinical course characterized by local recurrence and/or dissemination to other epithelial sites, leading to death within 6-12 months after the initial diagnosis despite surgery and aggressive antineoplastic treatment. These data suggest a novel variant of peripheral T-cell lymphoma operationally characterized as primary gastric, apoptosis-rich, CD103+, EBV-, T-cell lymphoma co-expressing CD4, CD8, CD16 and cytotoxic molecules.

Adult↗
PubMed2000

Comparative genomic hybridization: uses and limitations.

Comparative genomic hybridization (CGH) has contributed significantly to the current knowledge of genomic alterations in hematologic malignancies. Characteristic patterns of genomic imbalances not only have confirmed recent classification schemes in non-Hodgkin's lymphoma, but they provide a basis for the successful identification of genes with previously unrecognized pathogenic roles in the development of different lymphomas. Based on its technical limitations, there is little reason to apply CGH to chromosomes of metaphase cells in routine diagnostic settings. However, the new approach of CGH to DNA microarrays, a procedure termed matrix-CGH, overcomes most of the limitations and opens new approaches for diagnostics and identification of genetically defined leukemia and lymphoma subgroups. Current efforts to develop leukemia specific matrix-CGH DNA chips, which are designed to meet the clinical needs, are presented and discussed.

Hematologic Neoplasms↗